Next Article in Journal
FOXK2 Transcription Factor and Its Emerging Roles in Cancer
Next Article in Special Issue
Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10
Previous Article in Journal
A Systematic Pan-Cancer Analysis of Genetic Heterogeneity Reveals Associations with Epigenetic Modifiers
Previous Article in Special Issue
Triple Negative Breast Cancer Profile, from Gene to microRNA, in Relation to Ethnicity
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle

Targeting the mDia Formin-Assembled Cytoskeleton Is an Effective Anti-Invasion Strategy in Adult High-Grade Glioma Patient-Derived Neurospheres

1
Department of Cancer Biology, University of Toledo Health Science Campus, Toledo, OH 43614, USA
2
Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI 49503, USA
3
Department of Neurosurgery, ProMedica Hospital, Toledo, OH 43606, USA
4
Division of Neurosurgery, Department of Surgery, University of Toledo Medical Center, Toledo, OH 43614, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Deceased.
Cancers 2019, 11(3), 392; https://doi.org/10.3390/cancers11030392
Received: 23 January 2019 / Revised: 4 March 2019 / Accepted: 15 March 2019 / Published: 20 March 2019
(This article belongs to the Special Issue Cancer Invasion and Metastasis)
  |  
PDF [14564 KB, uploaded 20 March 2019]
  |  

Abstract

High-grade glioma (HGG, WHO Grade III–IV) accounts for the majority of adult primary malignant brain tumors. Failure of current therapies to target invasive glioma cells partly explains the minimal survival advantages: invasive tumors lack easily-defined surgical margins, and are inherently more chemo- and radioresistant. Much work centers upon Rho GTPase-mediated glioma invasion, yet downstream Rho effector roles are poorly understood and represent potential therapeutic targets. The roles for the mammalian Diaphanous (mDia)-related formin family of Rho effectors have emerged in invasive/metastatic disease. mDias assemble linear F-actin to promote protrusive cytoskeletal structures underlying tumor cell invasion. Small molecule mDia intramimic (IMM) agonists induced mDia functional activities including F-actin polymerization. mDia agonism inhibited polarized migration in Glioblastoma (WHO Grade IV) cells in three-dimensional (3D) in vitro and rat brain slice models. Here, we evaluate whether clinically-relevant high-grade glioma patient-derived neuro-sphere invasion is sensitive to formin agonism. Surgical HGG samples were dissociated, briefly grown as monolayers, and spontaneously formed non-adherent neuro-spheres. IMM treatment dramatically inhibited HGG patient neuro-sphere invasion, both at neuro-sphere embedding and mid-invasion assay, inducing an amoeboid morphology in neuro-sphere edge cells, while inhibiting actin- and tubulin-enriched tumor microtube formation. Thus, mDia agonism effectively disrupts multiple aspects of patient-derived HGG neuro-sphere invasion. View Full-Text
Keywords: high-grade glioma 1; glioblastoma 2; invasion 3; tumor microtubes 4; formin 5; actin 6 high-grade glioma 1; glioblastoma 2; invasion 3; tumor microtubes 4; formin 5; actin 6
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Pettee, K.M.; Becker, K.N.; Alberts, A.S.; Reinard, K.A.; Schroeder, J.L.; Eisenmann, K.M. Targeting the mDia Formin-Assembled Cytoskeleton Is an Effective Anti-Invasion Strategy in Adult High-Grade Glioma Patient-Derived Neurospheres. Cancers 2019, 11, 392.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top